Sánchez Ferrer, Álvaro

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Sánchez Ferrer, Álvaro

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Sánchez Ferrer, Álvaro

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Universidad de Murcia. Departamento de Bioquímica y Biología Molecular A

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Open Access
Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice
(Wiley, 2021-03-16) Zapata- Pérez, Rubén; Tammaro, Alessandra; Schomakers, Bauke V.; Scantlebery, Angelique M. L.; Denis, Simone; Elfrink, Hyung L.; Giroud- Gerbetant, Judith; Cantó, Carles; López Leonardo, Carmen; McIntyre, Rebecca L.; Weeghel, Michel van; Sánchez Ferrer, Álvaro; Houtkooper, Riekelt H.; Química Orgánica; Bioquímica y Biología Molecular A; Facultad de Química; Facultad de Veterinaria
Nicotinamide adenine dinucleotide (NAD+) homeostasis is constantly compromised due to degradation by NAD+-dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.
Open Access
Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins
(Nature Research, 2016-07-01) Martín Sánchez, María Rosario Fátima; Tyrkalska, Sylwia D.; Candel Camacho, Sergio; Angosto, Diego; Gómez Abellán, Victoria; García Moreno, Diana; Zapata Pérez, Rubén; Sánchez Ferrer, Álvaro; Pelegrín Vivancos, Pablo; Mulero Méndez, Victoriano Francisco; Sepulcre Cortés, María Pilar; Farmacología
Inflammasomes are cytosolic molecular platforms that alert the immune system about thepresence of infection. Here we report that zebrafish guanylate-binding protein 4 (Gbp4),an IFNg-inducible GTPase protein harbouring a C-terminal CARD domain, is required for theinflammasome-dependent clearance of Salmonella Typhimurium (ST) by neutrophils in vivo.Despite the presence of the CARD domain, Gbp4 requires the universal inflammasomeadaptor Asc for mediating its antibacterial function. In addition, the GTPase activity of Gbp4is indispensable for inflammasome activation and ST clearance. Mechanistically, neutrophilsare recruited to the infection site through the inflammasome-independent production of thechemokine (CXC motif) ligand 8 and leukotriene B4, and then mediate bacterial clearancethrough the Gbp4 inflammasome-dependent biosynthesis of prostaglandin D2. Our resultspoint to GBPs as key inflammasome adaptors required for prostaglandin biosynthesis andbacterial clearance by neutrophils and suggest that transient activation of the inflammasomemay be used to treat bacterial infections.
Open Access
A ribonuclease III involved in virulence of Mucorales fungi has evolved to cut exclusively single-stranded RNA
(2021) Falk, Sebastian; Zapata Pérez, Rubén; Sánchez Ferrer, Álvaro; Nicolás Molina, Francisco Esteban; Sánchez Ferrer, Álvaro; Navarro Ros, Eusebio; Garre Mula, Victoriano; Padmanabhan Iyer, Subramanian; Cánovas Márquez, José Tomás; Genética y Microbiología
Open Access
In vitro, in vivo, and in silico evidence for the use of plant pigments betalains as potential nutraceuticals against Alzheimer’s disease
(Wiley, 2024-07-24) Martínez-Rodriguez, Pedro; Henarejos Escudero, Paula; Hernández García, Samanta; Gandía Herrero, Fernando; Sánchez Ferrer, Álvaro; Bioquímica y Biología Molecular A
Anti-amyloidogenic properties of plant pigments betalains as potential nutraceuticals against Alzheimer’s disease have been screened using 24 pure molecules. Twenty-two betalains reduced amyloid aggregation in vitro, eight of them up to 100%, with IC 50values in the micromolar range. Atomic force and transmission electron microscopy images showed the typical fibrils associated with Alzheimer’s disease and how beta-lains avoid its formation. Neuroprotection after ingestion was supported by in vivo experiments with Caenorhabditis elegans. Indoline-betacyanin was the most effective molecule by significantly improving the chemotactic behavior of the CL2355 strain,a model of Alzheimer’s disease. Furthermore, in-depth molecular docking analyses revealed that the pigments interact with the N-terminal region of the amyloid pep-tide. This work is the most comprehensive study in the field and provides in vitro, in vivo, and in silico evidence for the use of betalains as nutraceuticals of relevance in theprevention of Alzheimer’s disease
Open Access
A predictive model for hospitalization and survival to COVID‑19 in a retrospective population‑based study
(Nature Research, 2022-10-28) Cisterna García, Alejandro; Guillén Teruel, Antonio; Caracena, Marcos; Pérez-Cuadrado Martínez, Enrique; Jiménez Barrionuevo, Fernando; Francisco Verdú, Francisco J.; Reina, Gabriel; González Billalabeitia, Enrique; Palma Méndez, José Tomás; Sánchez Ferrer, Álvaro; Botía Blaya, Juan Antonio; Ingeniería de la Información y las Comunicaciones; Facultades de la UMU::Facultad de Informática
The development of tools that provide early triage of COVID-19 patients with minimal use of diagnostic tests, based on easily accessible data, can be of vital importance in reducing COVID-19 mortality rates during high-incidence scenarios. This work proposes a machine learning model to predict mortality and risk of hospitalization using both 2 simple demographic features and 19 comorbidities obtained from 86,867 electronic medical records of COVID-19 patients, and a new method (LR-IPIP) designed to deal with data imbalance problems. The model was able to predict with high accuracy (90–93%, ROC-AUC = 0.94) the patient's final status (deceased or discharged), while its accuracy was medium (71–73%, ROC-AUC = 0.75) with respect to the risk of hospitalization. The most relevant characteristics for these models were age, sex, number of comorbidities, osteoarthritis, obesity, depression, and renal failure. Finally, to facilitate its use by clinicians, a user-friendly website has been developed (https://alejandrocisterna.shinyapps.io/PROVIA).
Open Access
The first comprehensive phylogenetic and biochemical analysis of NADH diphosphatases reveals that the enzyme from Tuber melanosporum is highly active towards NAD+
(Nature Research, 2019) García-Saura, Antonio Ginés; Zapata-Pérez, Rubén; Martínez-Moñino, Ana Belén; Francisco Hidalgo, José; Morte Gómez, María Asunción; Pérez Gilabert, Manuela; Sánchez Ferrer, Álvaro; Bioquímica y Biología Molecular A
Las hidrolasas Nudix (por nucleósido difosfatasas unidas a otros motivos, X) son una familia diversa de proteínas capaces de escindir una enorme variedad de sustratos, que van desde azúcares nucleotídicos hasta ARNs coronados con NAD+. Aunque todos los miembros de esta superfamilia comparten un motivo catalítico común conservado, la caja Nudix, su especificidad de sustrato radica en rasgos de secuencia específicos, que dan lugar a diferentes subfamilias. Entre ellas, las NADH pirofosfatasas o difosfatasas (NADDs) están poco estudiadas y no se sabe nada de su distribución. Para solucionar esto, diseñamos un patrón compatible con Prosite para identificar nuevas secuencias de NADDs. El escaneo in silico de la base de datos UniProtKB mostró que el 3% de las proteínas Nudix eran NADDs y mostraban 21 arquitecturas de dominio diferentes, siendo la arquitectura canónica (NUDIX-like_zf-NADH-PPase_NUDIX) la más abundante (53%). Curiosamente, las secuencias fúngicas de NADD destacaban entre los eucariotas y se distribuían en varias clases, incluyendo los Pezizomicetos. Inesperadamente, en esta última Clase de hongos, se encontró que los NADDs estaban presentes desde el ancestro reciente más común hasta las Tuberaceae, siguiendo una distribución de la filogenia molecular similar a la descrita previamente usando dos mil genes individuales concatenados. Por último, cuando se caracterizó bioquímicamente la NADD de Tuber melanosporum, formadora de trufas, ésta mostró la mayor relación de eficiencia catalítica NAD+/NADH jamás descrita. .
Metadata only
Estudio de la polifenol oxidasa de uva monastrell : purificación, caracterización y latencia / Alvaro Sánchez Ferrer ; director Francisco García Carmona.
(Murcia : Universidad de Murcia, facultad de Biología,, 1989) Sánchez Ferrer, Álvaro; García Carmona, Francisco
Open Access
Cinética de hidroxilación y oxidación de compuestos fenólicos por Polifenol Oxidasa de uva Monastrell (Vitis Vinifera)
(Murcia: Universidad de Murcia, Servicio de Publicaciones, 1987) Sánchez Ferrer, Álvaro; Cabanes Cos, Juana; Bru Martínez, Roque; Facultad de Biología
La enzima polifenol oxidasa ha sido purificada a partir de uva Monastrell mostrando actividad tanto en la oxidación de monofenoles (cresolasa) como en la de o-difenoles (catecolasa). Los parámetros cinéticos, Km y temperatura óptima, han sido evaluados en ambas actividades. La actividad cresolasa presenta un período de retardo característico, que puede ser modificado por la temperatura, la concentración de enzima, la presencia de o-difenoles y la concentración de sustrato.